In India, the world's largest democracy and second most populous country, malaria remains an enormous public health problem. The National Institute of Malaria Research (NIMR) in New Delhi is the only institute in India dedicated to finding short- and long-term solutions to the problem of malaria through basic, applied, and operational field research. The Center for the Study of Complex Malaria in India (CSCMi) will bring together a group of leading US experts in the fields of malaria parasite research to work in tandem with faculty at the NIMR. Malaria in India is 'complex'; two predominant species of parasite infect almost equal numbers of people, and may be present serially or concurrently in one person. Each species also has multiple strains (genotypes) that can serially or concurrently infect. Indian malaria complexity, its variation by location, and its consequences for malaria severity and transmission, are the research focus of the CSCMi, which aims to develop the knowledge, tools, and evidence-based strategies needed to support the intervention and control programs of Indian government organizations, and to build research capacity in India and help train its next generation of malaria and mosquito vector biologists. CSCMi research comprises three Projects: 1) Epidemiology, 2) Transmission, and 3) Pathology and Diagnosis. Project 1 will rely on multiple blood samples from 3000 (1000 x 3) longitudinally-tracked individuals, both symptomatic and asymptomatic for different malarias, recruited at three ecologically and epidemiologically diverse NIMR field sites. It will assess how infection complexity, parasite diversity, and transmission rate impact immunity. Project 2 will investigate ecological and evolutionary determinants of malaria transmission, and the efficacy of novel evolution-proof bio-insecticides for disrupting transmission of simple and complex malaria. Project 3 will deploy next-generation genomics to study multiplicity of infection and the rise of antimalarial drug-resistant clones, and to develop a diagnostic test for drug-resistant parasites. CSCMi projects will be supported by Administrative, Data Management, and Genomics Cores to be located at the NIMR's new facility in Dwarka, New Delhi.